Method for the manufacture of the disodium salt of ethylenediaminetetraacetic acid

ABSTRACT

A process for making partial salts of polycarboxylic polyamino acid chelating agent compounds characterized by forming a solution of a polyamino polycarboxylic acid salt adjusting it to a pH level above the normal pH of the salt which it is desired to produce, evaporating, and separating from the mother liquor the desired partial salt which crystallized first thereby salvaging a useful mother liquor, producing a crystalline partial salt of the chelating agent which has the characteristic of being capable of going into aqueous solution in subsequent use at a rate far greater than partial salts prepared by conventional neutralization technique.

United States Patent Continuation-impart of application Ser. No.716,003, Mar. 26, 1968, now abandoned which is a continuation-in-part ofapplication Ser. No. 660,135, Aug. 11, 1967, now abandoned which is acontinuation of application Ser. No. 382,947, July 15, 1964, nowabandoned.

[54] METHOD FOR THE MANUFACTURE OF THE DISODIUM SALT 0FETHYLENEDIAMINETETRAACETIC ACID 4 Claims, No Drawings [52] US. Cl260/534 E [51] Int. Cl... ..C07c10l/20, C07c 101/26 [50] Field of Search260/534 E OTHER REFERENCES Kubias, Chemical Abstracts Vol.44:8824(f)1950 Primary Examiner- Lewis Gotts AssistantExaminer-Jacqueline L. Davison A!t0rneyThomas B. Graham ABSTRACT: Aprocess for making partial salts of polycarboxylic polyamino acidchelating agent compounds characterized by forming a solution of apolyamino polycarboxylic acid salt adjusting it to a pH level above thenormal pH of the salt which it is desired to produce, evaporating, andseparating from the mother liquor the desired partial salt whichcrystallized first thereby salvaging a useful mother liquor, producing acrystalline partial salt of the chelating agent which has thecharacteristic of being capable of going into aqueous solution insubsequent use at a rate far greater than partial salts prepared byconventional neutralization technique.

METHOD FOR THE MANUFACTURE OF THE DISODIUM SALT OFETHYLENEDIAMINETETRAACETIC ACID HISTORY OF THE APPLICATION Thisapplication is a continuation-in-part of our application Ser. No 716,003, filed March 26, 1968, now abandoned which in turn is acontinuation-in-part of our application Ser. No. 660,135, filed Aug.11-, 1967 now abandoned which in turn was a continuation of ourapplication Ser. No. 382,947, filed July 15, 1964, now abandoned.

This invention is concerned with a method for the preparation ofpartially neutralized salts of polyfunctional amino carboxulic acids,such as ethylene diamine tetraacetic acid and nitrilo triacetic acid,particularly those salts which are l and 2 alkali metal units away fromfull neutralization of all acid positions.

Commonly, ethylene diamine tetraacetic acid is made by the condensationof ethylene diamine with formaldehyde and cyanide in a strongly alkalinemedium to produce an alkaline salt containing about 40percent ofethylene diamine tetraacetic acid. This is well exemplified in the U.S.Pat. No.

2,407,645, Bersworth.

Where ethylene diamine tetraacetonitrile or nitrilo triacetonitrile arefirst formed as precursor compounds, for example,as set for the U.S.Pat. No. 2,855,428, Singer and Weisberg, the preparation of the ethylenediamine tetraacetic acid or the nitrilo triacetic acid salts is a resultof a hydrolysis operation and commonly the product will contain somealkali.

When it is desirable to prepare the disodium salt of ethylene diaminetetraacetic acid, it can be done by mixing sodium hydroxide flake withan appropriate molar amount of ethylene diamine tetraacetic acidcontaining about -15 percent water. This mixture is blended in the drystate and the heat of reaction is sufficient to evaporate the moisture,thereby producing a blend which is the disodium salts of EDTA. It can befurther vacuum dried or air dried.

in a wet method of preparation, ethylene diamine tetraacetic acid isadded to a dilute solution of sodium hydroxide until a pH of about 4.7is reached; the solution ordinarily will be clear at this point. Thissolution is boiled until crystallization occurs and is then cooled veryslowly. The resulting crystals are filtered or centrifuged off andvacuum or air dried. Following a similar procedure in preparing a clearsolution by reaction of sodium hydroxide with acid, the solution can bespray dried.

it should be self-evident that any of these techniques which involvecareful balancing of the reactants, time for reaction and, further, timefor recovering the product, are cumbersome to the point of beingundesirable when commercial application is necessary.

Accordingly, a fundamental object of our invention is to provide a basictechnique to carry out crystallization to prepare compounds of ethylenediamine tetraacetic acid and nitrilo triacetic acid in neutral orslightly acid form, that is, l or 2 alkali metal moieties short of fullneutralization of all acid hydrogens.

Other objects and advantages of the invention will in part be obviousand in part appear hereinafter.

Our invention, therefore, involves a technique of crystallizing thedisodium salt of ethylene diamine tetraacetic acid from a solutioncomposed of both ethylene diamine tetraacetic acid Na salt and ethylenediamine tetraacetic acid Na; salt. We have found that the material whichcrystallizes from this buffer solution is extremely pure, has welldefined crystalline structure, has a rate of solution conspicuouslygreater than ethylene diamine tetraacetic acid Na salt crystallized fromsolutions of Na ethylene diamine tetraacetic acid. The materialcrystallized from the buffer solution which ranges from chemicalneutrality to slightly alkaline, pH 6.8-7.5, exhibits the expected pHfor Na salt, pH 5.5, when it is dissolved in pure water.

The following procedure produces Na ethylene diamine tetraacetic aciddihydrate of excellent purity, of high rate of solubility with thebyproduct being a solution consisting largely of Na ethylene diaminetetraacetic acid, but containing some Na ethylene diamine tetraaceticacid. The mother liquor has the surprising characteristic of possessinga higher chelating power per gram of saturated solution than it ispossible to get from either a straight solution of either pure Nagethylene diamine tetraacetic acid or pure Na; ethylene diaminetetraacetic acid, and indicates a marked deviation (approximately 23percent) from expected solubility of N33 salt.

Thus, it will be seen that fundamentally, our process involves providinga medium in which the sodium salt (alkali metal salt) of ethylenediamine tetraacetic acid is in solution, adding sufficient sodiumhydroxide (alkali metal hydroxide) to bring the pH to a range of6.8-7.5, and preferably 7.0-7.3, and then evaporating and concentratingthe solution at a pH level corresponding to that of the salt desired.Thus, the sodium salt desired is crystallized from a buffered medium andapparently, because it is in a buffered medium a theoretical saltrelationship with hydrated product is produced.

The following example will develop the stoichiometric relationships ingreater detail. 7

EXAMPLE l To 5,000 parts of 38 percent aqueous solution of ethylenediamine tetraacetic acid Na, (5 part-moles) at 95 C. is added 1,000parts of solid ethylene diamine tetraacetic acid (3.42 part-moles).Unless the free caustic content of the Na, solution is excessively high,the pH of the resulting slurry should be between 6.8-7.5 and preferably7.07.3. lf higher than this, more acid should be added to reduce the pHto 7.5. The slurry is then boiled until 2,000 parts of water have beenremoved. The slurry is then cooled and filtered. The filtrate asindicated from pH or from chelating power is essentially ethylenediamine tetraacetic acid Na salt containing only relatively smallamounts of disodium salt. I

It must also be understood that all commercial solutions of Na, ethylenediamine tetraacetic acid contain free caustic to an extent which mayvary from it to 3 percent. Presence of this free caustic lowers Na saltyields to some extent and produces a higher ratio of Na;, salts insolution.

If less acid is used to neutralize, the Na, salt yields will drop andthe amount of mother liquor remaining will increase. It is usually notpracticable to attempt to precipitate the Na; salt from a solution whichcontains more than 50 percent mole ratio basis of Na; salt.

If more solid ethylene diamine tetraacetic acid is used, the pH of themother liquor will drop and while the yield of disodium salt willincrease, solubility characteristics will approach those of the Na; saltprepared by neutralizing ethylene diamine tetraacetic acid with causticin a pure water solution. It is generally considered impractical toprepare the rapidly dissolving Na from solutions which contain more than5 moles of disodium to l of N21,. This should not, however, beconsidered a limit since even the presence of small amounts of Na; saltduring the crystallization operation will tend to increase the rate ofsolubility of the Na; salt crystals which are formed.

This method of manufacture of ethylene diamine tetraacetic acid Na, salthas several advantages over the three methods presently being used.

The dry mix method, using only small amounts of water, economicallyproduces a product using a minimum of production time and yields noliquor to be disposed of. However, since the amount of water used isvery limited, the reaction is frequently incomplete and the resultingproduct is actually a mixture of unreacted ethylene diamine tetraaceticacid, ethylene diamine tetraacetic acid Na, salt, ethylene diaminetetraacetic acid Na, salt, and ethylene diamine tetraacetic acid Na,salt. Furthermore, the product is very slow in dissolving. Our newmethod produces a homogeneous product which dissolves extremely rapidly.

The wet method, the second outlined above, products a product of veryhigh purity. However, production time required for this material is verylong and the product is also slow in dissolving. Our new method requiresmuch less production time and the product has a high rate of solution.

The third method, indicated above, is used only when a product having avery rapid rate of solution is desired since the production costs arevery high due to the spray-drying operation. Our method avoids thiscostly operation and produces a product having a rate of solution atleast as good, but usually greater than that produced by spray drying.

Our method has one additional advantage over any of the three presentlyused processes. Each of these used ethylene diamine tetraacetic acid asthe source ethylene diamine tetraacetic acid. In our method, only 40percent of the ethylene diamine tetraacetic acid comes from the acid,the remaining 60 percent being from 38 percent ethylene diaminetetraacetic acid Na, solution. Since the latter is the cheapercommercial source of ethylene diamine tetraacetic acid, this is anadditional cost saving feature of our method. The salt is available inthis form because it is produced directly as such solution in the methoddescribed in U.S. Pat. No. 2,407,645.

For aid in extending the example to preparation of other salts, thefollowing pH data on ethylene diamine tetraacetic acid and nitrilotriacetic acid are useful:

Salt pH EDTA Na,

Na 7.5 Na, 5.5

NTA Na Following the procedure of example I, it is possible to prepareany of the alkali metal salts of ethylene diamine tetraacetic acid andnitrilo triacetic acid. The procedure can be extended further todiethylene triamine pentaacetic acid and tetraethylene pentaminehexacetic acid. It will be noted that these compounds merely add anethylene amine moiety to the EDTA. Similarly, salts of hydroxyethylvariants of those compounds may be prepared, provided, no more thanabout one-half of the acetic acid moieties are replaced by hydroxyethylgroups; thus, hydroxyethyl ethylene diamine triacetic acid; hydroxyethyldiethylene triamine pentaacetic acid; hydroxyethyl triethylene pentaminehexacetic acid, etc. The potassium salts are prepared in the samefashion as the sodium salts and, inasmuch as the pH of the severalalkali metal salts does not differ materially from the pH of the sodiumsalts, the procedure is the same.

Basic to the operation is the matter of starting with a solution of thesalt of the acid to be prepared. Commonly, this is the fully neutralizedsalt, as it comes from the process in which it is prepared. The processis made operable, and conveniently so, because the polyfunctional acidform of the NTA, EDTA and multiples thereof are good buffers. Thus, theycan be neutralized to the pH level desired and will hold the pH quitewell while water is removed and crystallization of the partiallyneutralized salt occurs.

Thus, for example, nitrilo triacetic acid disodium salt may be preparedby admixing 100 parts of solid nitrilo triacetic acid with 500 parts ofa 38 percent, by weight, aqueous solution of nitrilo triacetic acidtrisodium salt at 90 C.-95' C. to produce a slurry having a pH level of7.0-7.3. The resulting slurry is boiled to dissolve the acid andevaporated to a suitable concentration whereupon, on cooling, theprecipitated disodium salt is readily recovered.

EXAMPLE ll ethylenediamine tetraacetic acid Na at 70 C. was admixed.

with 400 parts of water and parts of ethylenediamine tetraacetic acid.This yielded a slurry of pH 7.0-7.3. The slurry was boiled until about200 parts of water had been removed whereupon it was cooled, filtered,and washed, resulting in the recovery of the disodium salt.

The prior art disodium salt was prepared by means of the followingprocedure:

10 moles of ethylene diamine as a 30 percent aqueous solution and 4moles of solid caustic soda were placed in a steamheated kettle suppliedwith an agitator. Eight moles of sodium cyanide as a concentrated watersolution (about 30 percent) were added and the solution heated to 60 C.About a 10-inch vacuum was applied to bring the liquid to incipientboiling. Formaldehyde (7.5 moles of 37-40 percent aqueous solution) wasslowly added, the temperature being held at 60 C., and the solutionvigorously stirred. Then, when the evolution of ammonia hassubstantially stopped, 8 more moles of sodium cyanide, followed by 8moles of formaldehyde was added as before. This was continued until 40moles of cyanide and 40 moles of formaldehyde had been added. Then atthe end about 2 moles more of formaldehyde were added, making 42 in all,to remove any last traces of cyanide. About 8 to 10 hours were requiredto complete the reaction. The resulting product, referred to herein asthe crude reaction product was essentially an aqueous solution of thetetrasodium salt of ethylene diamine tetraacetic acid.

Thereafter, 1,000 grams of the crude reaction product, i.e. a 25percent, by weight, aqueous solution of EDTA Na. were added to 264 gramsof ethylene diamine tetraacetic acid; the pH level of the system being4.1. The mixture which had initially gelled and was therefore thinned,was heated to boiling and allowed to cool and crystallize. The formeddisodium crystals were then filtered, washed and dried.

The solubility of each of these materials was determined by admixing therespective salts, under constant agitation at a temperature of 20-22 C.,with sufficient distilled water to make a 9 percent, by weight, solutionof the salt and noting the time required for total solubility to occur,the latter state being determined by the clarity of the solution.

As a result, the disodium salt of this invention completely dissolved in2 minutes while the prior art material did not exhibit total solubilityafter an agitation period in excess of 2 days. The surprising solubilitydifferences thus noted are a clear indication of the advantages to bederived from the practice of the novel process of this invention and,furthermore, lend great weight to the distinctions between the subjectprocess and the prior art; notably the pH differences.

EXAMPLE "I Additional commercial forms of the disodium salt ofethylenediamine tetraacetic acid were also tested for their solubilitycharacteristics by means of the procedure described in example ll,hereinabove.

The products tested included:

HCC powder-prepared by reacting under agitation 2 moles of flake causticsoda with 1 mole of damp ethylenediamine tetraacetic acid and thenheating to produce the dry powder product.

Sequestrene Na -prepared by reacting EDTA acid, water and NaOH sothat'at boil, a solution of approximately 28 percent concentration andhaving a pH level of 4.5 5.5 results which upon cooling yields thecrystalline products.

F.S. disodium-prepared by reacting 2 moles of 50 percent causticsolution with one mole of EDTA acid which had been slurried with hotwater so that at boil, the solution is of 25 percent concentration andthen filtering, cooling and drying crystalline product.

Spray dried product-prepared in same manner as F.S. disodium with theexception hat clear solution is spray dried instead of being chilled andcrystallized.

Commercial product-prepared by reacting dry or damp EDTA acid with a hot38 percent solution of EDTA Na,-EDTA acid added under agitation at 80C., until pH level reaches 5.25.4-slurry then cooled, centrifuged anddried.

TABLE Time Required for a Solution The results in the tabulation speakfor themselves despite the fact that the disodium salt, for example,prepared in ac- ..cordance with the example I shows no chemicaldifference from disodium salt, or a mixture which would analyze asdisodium salt, prepared by any other method. There appears to be somesubtle effect on the crystal structure induced by the instant method ofcrystallization which causes the material to dissolve in water far morerapidly than conventional known material.

What is claimed is:

l. A process for the production of a disalt of a compound selected fromthe group consisting of nitrilo triacetic acid, ethylene diaminetetraacetic acid, diethylene triamine pentaacetic acid and variants ofthose acids wherein not more than one-half of the acetic acid moietiesare replaced by hydroxy ethyl groups, comprising providing a solution ofthe salt fully neutralized, adding thereto solid-free acid in an amountsufficient to neutralize an amount of the salt to the predeterminedlevel, the resulting mixture having a pH level of from about 6.8 to 7.5,boiling said mixture of solid and salt solution to dissolve the solidacid and continuing boiling the solution to evaporate at least part ofthe water, and separating i the salt crystals formed in the medium.

2. A process in accordance with claim 1 for the production of disodiumsalt of ethylene diamine tetraacetic acid which comprises providing asolution of the tetrasodium salt of ethylene diamine tetraacetic acid,adding thereto solid-free acid in acid form and in amount to develop asolution of pH of 7.0-7.3, boiling said mixture of solid acid crystalsand salt solution to form a solution and to evaporate at least part ofthe water and then separating the disodium salt crystals formed in themedium.

3. A method in accordance with claim 2 wherein the free solidethylenediaminetetraacetic acid is added to an alkaline solution ofabout 40 percent concentration, the relative amounts being about 1 partof solid acid to 5 parts of solution, by weight.

4. A process in accordance with claim 1 for the production of nitrilotriacetic acid disodium salt wherein solid nitrilo triacetic acid isadded to a 38 percent nitrilo triacetic acid trisodium salt aqueoussolution at C.- C. to produce a slurry of solution pH 7.0-7.3, boilingsaid slurry to dissolve the acid and evaporating to a suitableconcentration, and then cooling and recovering precipitated di-sodiumsalt.

2. A process in accordance with claim 1 for the production of disodiumsalt of ethylene diamine tetraacetic acid which comprises providing asolution of the tetrasodium salt of ethylene diamine tetraacetic acid,adding thereto solid-free acid in acid form and in amount to develop asolution of pH of 7.0-7.3, boiling said mixture of solid acid crystalsand salt solution to form a solution and to evaporate at least part ofthe water and then separating the disodium salt crystals formed in themedium.
 3. A method in accordance with claim 2 wherein the free solidethylenediaminetetraacetic acid is added to an alkaline solution ofabout 40 percent concentration, the relative amounts being about 1 partof solid acid to 5 parts of solution, by weight.
 4. A process inaccordance with claim 1 for the production of nitrilo triacetic aciddisodium salt wherein solid nitrilo triacetic acid is added to a 38percent nitrilo triacetic acid trisodium salt aqueous solution at 90*C.- 95* C. to produce a slurry of solution pH 7.0- 7.3, boiling saidslurry to dissolve the acid and evaporating to a suitable concentration,and then cooling and recovering precipitated di-sodium salt.